Expressive

rs11129987 (ZNF662): Height-Associated Genetic Variant

Key takeaways

  • rs11129987 near ZNF662 (zinc finger protein 662) is one of 12,111 common variants linked to adult height in the largest height genetics study ever conducted
  • The identifying study analyzed DNA from 5.4 million people across European, East Asian, Hispanic, African, and South Asian ancestry groups
  • These height variants together account for roughly 40-45% of the genetic contribution to height in people of European ancestry
  • This variant is linked to altered gene expression in multiple brain regions, the sigmoid colon, and subcutaneous fat tissue

Key takeaways

  • rs11129987 near ZNF662 (zinc finger protein 662) is one of 12,111 common variants linked to adult height in the largest height genetics study ever conducted
  • The identifying study analyzed DNA from 5.4 million people across European, East Asian, Hispanic, African, and South Asian ancestry groups
  • These height variants together account for roughly 40-45% of the genetic contribution to height in people of European ancestry
  • This variant is linked to altered gene expression in multiple brain regions, the sigmoid colon, and subcutaneous fat tissue

What the research says rs11129987 was identified as one of 12,111 independent genome-wide-significant variants in a meta-analysis of 5.4 million individuals from 281 studies, spanning five major ancestry groups. The 12,111 variants cluster into 7,209 non-overlapping genomic segments covering approximately 21% of the genome, and collectively account for about 40% of phenotypic variance in height in European-ancestry populations (about 45% when all variants in the HapMap3 reference panel are included). Effect sizes and associated genomic regions were broadly consistent across ancestry groups, though prediction accuracy in non-European populations reached only about 10-24%, a difference attributed to linkage disequilibrium structure and allele frequency patterns rather than different causal variants.

Reported associations

  • Adult height: one of 12,111 common variants jointly accounting for close to all common-SNP-based heritability of adult height, with the full set explaining roughly 40-45% of phenotypic variance in European-ancestry populations; identified in a multi-ancestry meta-analysis of 5.4 million individuals

Evidence quality The height association comes from the largest published height GWAS to date, with 5.4 million participants from 281 contributing studies. The discovery sample was approximately 76% European ancestry, with additional representation from East Asian (about 9%), Hispanic/admixed (about 8.5%), African (about 5.5%), and South Asian (about 1.4%) groups. The study reports genome-wide-significant associations for 12,111 independent SNPs as a set; individual per-SNP effect sizes are not reported for specific variants in the available study text. Prediction accuracy using these variants in non-European populations is substantially lower (roughly 10-24% of variance) than in European-ancestry populations (40-45%), which the study attributes to differences in linkage disequilibrium and allele frequency rather than distinct causal variants. The authors characterize the common-variant association map for height as near-saturated for European-ancestry populations but note further work is needed for other ancestries.

Tissue-specific expression effects

  • HIGD1A: increased expression in the anterior cingulate cortex (brain), the nucleus accumbens (brain, basal ganglia), and the sigmoid colon GTEx Portal
  • CCDC13: reduced expression in the cerebellum and cerebellar hemisphere (brain) GTEx Portal
  • ENSG00000273328: reduced expression in non-sun-exposed skin and increased expression in subcutaneous adipose tissue GTEx Portal
  • HHATL: reduced expression in the caudate nucleus (brain, basal ganglia) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11129987?

rs11129987 is a common genetic variant located near the ZNF662 gene. It was identified as one of 12,111 variants significantly associated with adult height in a genome-wide study of 5.4 million people.

What gene is rs11129987 near?

rs11129987 is located near ZNF662, which encodes a zinc finger protein. The variant is also linked to expression changes in nearby genes including HIGD1A, CCDC13, and HHATL across multiple tissues.

How was rs11129987 discovered?

It was identified in a genome-wide association meta-analysis of 5.4 million individuals from 281 studies spanning five major ancestry groups. This is the largest height genetics study conducted to date.

Does rs11129987 affect gene expression in tissues beyond bone or muscle?

GTEx data links this variant to altered expression of HIGD1A in brain regions and the sigmoid colon, reduced CCDC13 expression in the cerebellum, differential ENSG00000273328 expression in skin and fat tissue, and reduced HHATL expression in the caudate nucleus. These are expression-level associations, and their functional significance in the context of height or other traits is not established.

Is rs11129987 equally predictive of height across all ancestry groups?

Effect sizes for this variant are broadly similar across ancestry groups, but overall height prediction accuracy is lower in non-European populations (roughly 10-24% of variance explained) compared to European-ancestry populations (roughly 40-45%). This difference is attributed to differences in local genetic variation patterns rather than different causal biology.